Endocrine Abstracts

JOINT3671

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor(NET) arising from parafolicular cells. It accounts for less than 5% of all thyroid tumors. The most characteristic feature of MTC is the production of calcitonin by tumor cells, turning it into a valuable tumor marker for diagnosis and follow up. Rare cases of calcitonin negative neuroendocrine tumors of the thyroid have been reported, and they represent a clinical challenge. We present 2 cases of unusual calcitonin negative MTC (CNMTC) First case is a 65 year old male, complaining with hoarseness and a neck mass, with suspicious lynph nodes in the neck and mediastinum, plus a vertebral T1 lesion on CT and PET scans sugestive of metastasis. FNA of the thyroid nodule was suspicious por MTC. Total thyroidcetomy plus neck and mediastinum disection was performed. T4aN1b M1 MTC was confirmed. Inmunohistochemistry (IHC) in the tumor was strongly possitive (+) for calcitonin, synaptophysin, CEA and TTF-1. No blood test for calcitonin was collected until three days after surgery, being undetectable at that point, and has remained so for the next 12 years of follow up, with also normal blood CEA levels, despite the bone lesion and a 2 cm suspicious mediastinum lymph node that persisted after surgery. Two years later, a pancreatic node newly appeared in scans and was finnally removed some after slowly growing on follow up with diagnosis of pancreatic NET G1PT2N0. Both the spine lesion and the neck were treated with radiotherapy after surgery and have remained stable, during follow up, without apperance of new lesions on multiple imaging tests performed. RET genetic testing in blood sample was inicially performed and negative and more recently NGS on tumor tissue showed no RET somatic mutations but a Gln61Arg mutation in HRAS gene. Case 2 is a 75 year old woman with an incidentally discovered thyroid nodule. Inicial FNA was suspicious for MTC, but her calcitonin serum levels were undetectable. A total thyroidectomy was performed and biopsy revealed a NET: IHC + for synaptophysin, TTF-1 and Cromogranin but negative for calcitonin, calcitonin related gen peptide and CEA. KI-67 index was 0,5%. Differential diagnosis was CNMTC or, less likely a thyroid metastases from another NET. A Galium PET scan showed no other lessions. Genetic testing in the tunor cells showed no mutations in RET nor in other genes tested (Oncomine panel).